Defense Date


Document Type


Degree Name

Doctor of Philosophy


Pharmaceutical Sciences

First Advisor

Norman V. Carroll, PhD, RPh

Second Advisor

Alexander N. Slade, MD, PhD

Third Advisor

Julie A. Patterson, PharmD, PhD

Fourth Advisor

Darcy P. Mays, PhD

Fifth Advisor

Pramit A. Nadpara, PhD, MS, BPharm


Background: Emerging evidence suggests that as more patients are surviving cancer, new persistent opioid use (no prior exposure to opioids before cancer therapy but requiring opioid prescriptions after curative intent treatment; NPOU) is of greater concern. In patients receiving curative intent radiation (definitive radiation therapy and as treatment for cure; CIR), the extent to which patients develop NPOU or continue opioid use (COU) following CIR is not known. Neither are factors associated with NPOU or COU, opioid doses, or time to discontinuation (TTD) of opioids in 5CS known. Objectives: Describe longitudinal trends opioid use in cancer survivors who received CIR, examine the association of NPOU and COU to patient specific factors as well as opioid dose levels and TTD of opioids. Methods: Electronic medical record data from individuals receiving CIR for any indication at Virginia Commonwealth University’s Massey Cancer Center in the last 11 years was used to create a longitudinal record of the oral morphine equivalent (OME) of prescriptions to determine NPOU and COU. Descriptive statistics as well as incidence, binomial logistic regressions, panel data models, mixed linear models, Kaplan Meyer survival curves and Cox proportional hazard models were used. Results: Based on our analysis, 5CS at this institution were prescribed high 30-day average daily OME doses (mean: 94, SD: 131) which increased from late 2009 to 2012, then decreased after 2012. Men, those of white compared to black race, those with public insurance, and patients with additional chemotherapy or no additional surgery appeared to be prescribed higher 30-day average daily OME doses between 2008 and 2018. Of 5CS who received CIR, 19.7% developed NPOU and 54.8% COU. Head and neck cancer, stage 3 disease, additional chemotherapy, African American race, certain insurance types, and comorbid conditions conferred increased odds of NPOU. Indigent insurance, anxiety, back pain, hypertension, and nicotine use were associated with increased odds of COU. Most 5CS do not utilize opioids long-term before or after CIR. 5CS with opioid prescriptions prior to radiation had sustained daily doses of 68.2 - 68.3 OMEs higher than those without opioid prescriptions. 5CS with public insurance, anxiety, depression, and other drug use were associated with higher average daily OMEs while diabetes and hypertension were associated with lower average daily OMEs. We predict that 5CS that undergo CIR will use at least some level of opioids, on average 4.1 daily OMEs one year after end of radiation. 5CS continue receiving opioid prescriptions for a median of 16.8 months after completion of CIR. Median TTD of opioids was shorter for patients without opioid exposure prior to therapy (NPOU; 13.0 months) compared to patients with opioid exposure prior to therapy (COU; 21.4 months). Factors associated with shorter TTD included NPOU and head and neck cancers. Conversely, additional surgery, death more than five years after diagnosis, as well as alcohol and nicotine use were associated with longer TTD of opioids. Discussion: Presence of comorbidities, substance use, and indigent or public insurance were associated with greater opioid burden, use, dose and length of time of opioid use. . Socioeconomic and health differences (African American race, indigent charity insurance, Medicaid, chronic conditions and substance use) in patients receiving CIR also result in increased opioid use, odds of NPOU and COU, opioid dose, and longer TTD of opioids. Conclusions: Our results have demonstrated substantial opioid use in cancer survivors. There are currently no evidence-based guidelines for opioid prescribing in cancer survivors. Guidelines to prevent misuse and opioid related deaths are warranted to prevent potential misuse due to high numbers of patients that continue to use opioids long after CIR, risk of NPOU, COU, and high OMEs utilized.


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